Cutting Edge: Expression of FcγRIIB Tempers Memory CD8 T Cell Function In Vivo

During reinfection, high-affinity IgG Abs form complexes with both soluble Ag and Ag displayed on the surface of infected cells. These interactions regulate cellular activation of both innate cells and B cells, which express specific combinations of activating Fc gamma Rs (Fc gamma RI, Fc gamma RIII, Fc gamma RIV) and/or the inhibitory Fc gamma R (Fc gamma RIIB). Direct proof for functional expression of Fc gamma R by Ag-specific CD8 T cells is lacking. In this article, we show that the majority of memory CD8 T cells generated by bacterial or viral infection express only Fc gamma RIIB, and that FcgRIIB could be detected on previously activated human CD8 T cells. Of note, Fc gamma R stimulation during in vivo Ag challenge not only inhibited the cytotoxicity of memory CD8 T cells against peptide-loaded or virus-infected targets, but Fc gamma RIIB blockade during homologous virus challenge enhanced the secondary CD8 T cell response. Thus, memory CD8 T cells intrinsically express a functional Fc gamma RIIB, permitting Ag-Ab complexes to regulate secondary CD8 T cell responses.